Chris Patil of Ouroboros is a postdoctoral fellow, currently working with Judith Campisi in the Life Sciences division of the Lawrence Berkeley National Lab. Here is Chris's response to the question I recently sent to a number of biogerontologists:

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The main purpose of ageing research at present is NOT to make people young and immortal as is often publicised in the media, but instead to prevent/combat disease and disability, allowing everyone to live healthier lives for longer. Is this media representation of ageing research detrimental to the true focus of ageing research? If you disagree with the main purpose of ageing research outlined in the question please state why?

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I don’t believe in a monolithic entity called “aging research”, and consequently I don’t believe that that entity has a “true focus”. Aging is a huge field; there are any number of ways to engage with it; there is consequently tremendous diversity among scientists who consider themselves to be involved in aging research. There are distinct sub-communities, certainly, which can be classified according to their priorities and focus; in comparisons between these sub-communities, patterns do emerge. For instance, I’ve noticed a tradeoff between immediacy and scope — that is, those whose work can benefit elderly people today tend to have fairly modest ambitions compared to those whose labors will take some time to bear fruit. A lot of this has to do with individual priorities, and where individual scientists feel like they can do the most good and/or do the work that makes them happiest.

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I feel most comfortable speaking for myself and my community — let’s call us “academic biogerontologists” -- whom I’m going to (conveniently) define as the set of individuals devoted primarily to the production of fundamental research in the biology of aging, who primarily work in universities or similarly organized institutions, and whose work is primarily published in peer-reviewed journals.

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For academic biogerontologists, there are two related aims of aging research. The explicit, near-term goal is improving our understanding of the aging process at multiple levels — at the cellular and molecular levels, but also (as tools get better) at the level of cell-cells interactions (i.e., tissues) as well as the gemisch of global gene expression studies that fall under the “systems biology” umbrella. The (occasionally) implicit, longer-term goal is to use this understanding to create interventions that will improve the health and happiness of human beings — and here the ambitions range from the treatment of single aging-related diseases to therapies that will delay or even reverse the aging process itself.

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For us, the two processes go hand in hand, and both are essential. Fundamental research into the mechanisms of aging is constantly revealing new connections between well-studied systems (like nutritional control of cell growth) and the basic biology of aging. It is from these connections, from this knowledge, that the interventionist tools of the future will emerge. Both sorts of work can and should be undertaken simultaneously, if not by the same groups then in an open community where there is a great deal of communication across the aisle, so that both types of scholars are learning from each other at an optimum rate. Indeed, we’re beginning to see some of the first pharmaceuticals developed by academic-industrial collaborations and academic spinoff companies; it’s an exciting time.

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One thing that we are constantly learning from basic studies is that as much as we know (especially, as much as we’ve learned in the past 15 years or so, a period that I think of as the dawning era of the modern biology of aging), we could always know more. One example is the recent discovery in model organisms that stem cells don’t function well in aged microenvironments — in aged niches, they either don’t regenerate well or become dysregulated; for those of you just joining us, having dysregulated telomerase-positive immortal cells in your body is potentially a fairly bad thing. These recent observations have caused us to seriously rethink the strategies that will be required to effectively use stem cell transplantation in the treatment of age-related disease. So I don’t think we’re ever going to reach the point where we can take off our gloves and say, “This is a solved problem; no more fundamental research for us!” Not that I think anyone is seriously advocating a moratorium on future basic studies, any more than they were advocating injecting old people with huge doses of undifferentiated cells. There are differences of opinion on the relative import of basic vs applied work but inasmuch as both fields are far smaller than they should be I don’t think the time has arrived for debating tradeoffs between the two.

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But I’ve digressed extensively. Do I think that media representations are positive or negative? To the extent that they spread the word in a measured way, like the piece in the Economist earlier this year. I think they’re largely positive. Even when individual articles get their “zing” from focusing on what I consider to be quite long-term goals, I think they still do a tremendous amount of good by raising consciousness about the biology of aging. We’re entering a period of history when people will become more and more willing to appreciate the benefit of long-term thinking, especially as related to technology — we’re already seeing that with the environment, and I think aging research and anti-aging medicine will be another example. One of my scientific heroes, Carl Sagan, popularized space exploration and even the nascent field of exobiology by making bold statements about the longest-term and wildest possibilities, and in so doing he inspired a generation of young scientists. I don’t see any reason why aging should be different: As long as we’re scientifically responsible, honest about the current state of affairs, and reasonable in our predictions, why shouldn’t we emphasize the long-term payoff of our work? Full steam ahead!

Soon to be up and running is my new blog, anti-ageing research, which focuses NOT on the biology of ageing, but the ideas and research aimed at preventing or treating the effects of the ageing process. Check it out.

I recently emailed a number of biogerontologists the following question:

The main purpose of ageing research at present is NOT to make people young and immortal as is often publicised in the media, but instead to prevent/combat disease and disability, allowing everyone to live healthier lives for longer. Is this media representation of ageing research detrimental to the true focus of ageing research? If you disagree with the main purpose of ageing research outlined in the question please state why?

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One of the first people to respond to this question was Aubrey de Grey with the following:

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Your premise is somewhat wide of the mark, in that most people who do research into aging actually regard any appreciable therapeutic benefit from their work as a very remote possibility (in both senses - unlikely, and very distant in time if it happens at all). Thus, their purpose is merely to **understand** aging, rather in the way that the purpose of meteorologists is to understand the weather, as opposed to actually doing anything about it.

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However, there is indeed a small but growing minority of gerontologists (including myself) who do identify the postponement of aging as our main purpose, not least because we are more optimistic than the majority of our colleagues with regard to the possibility of success. For us, you have it exactly right: the goal is to prevent people from going downhill as they become chronologically older. The problem is, we recognise that this will have a side-effect (which most of us regard as a side-benefit, but that's another issue altogether): people won't tend to die peacefully in their sleep either, any more than healthy 30-year-olds do, until and unless they get to an age at which the therapies we develop cease to work. Worse yet (he said, sarcastically), for those of us (like myself) who claim that the therapies that will first make a major impact on aging will be bona fide rejuvenation therapies, i.e. therapies that restore the molecular and cellular (and higher-order) structure of the body to something like the way it was in young adulthood, the situation is particularly extreme, because the likely rate at which such technologies will be improved following their initial development is such that the therapies will never cease to work: aging will be postponed faster than it occurs, so it will never catch up with us. (This is the phenomenon that I've termed "longevity escape velocity".) Thus, I predict that people's life expectancies will be determined only by their incidence of death from causes not related to their age, like accidents and nearby supernovae. That is the simple and inescapeable conclusion of the work I do. Clearly it means people still have a non-zero risk of death each year (or indeed each day) - but unfortunately it does sound awfully like immortality if you're the sort of journalist who wants to sell papers, so that's how it tends to get described.

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So to your main question: is this detrimental? Yes, I believe it is immensely detrimental. (I don't precisely blame the journalists in question, you understand - they're just doing what they're paid to do - but still.) Ultimately, the reason why calling my goal "immortality" sells papers is because it trivialises it - it confuses my work with something that we all know is impossible, i.e. the technological elimination of any risk of death. And an awful lot of people need that confusion - they need to be helped to believe that what I'm doing is really not science but just entertainment. Why do they need that? Because they've made their peace with aging. They've spent their lives in the situation where there was no hope for escaping this terrible, yet rather distant, fate - so they've had the choice of either (a) spending their time preoccupied by that, or (b) putting it out of their minds and getting on with their miserably short lives, making the best of a bad job. And of course the rational thing to do in such a situation, even if it entails quite unbelievably irrational rationalisations, is (b). So now this troublemaker comes along and says there may be a chance. Now, if I were saying "Hey, here is the actual therapy, today, proven and provided", there'd be no problem - just as when Pasteur worked out that hygiene was a good idea, or whatever. But unfortunately all I'm offering is a **chance** that in a few **decades** we will have that techniology. And an awful lot of people don't want to get their hopes up, for fear of having them dashed.... so they stick to what they know, their faith that aging really is still inevitable. But at the same time, they desperately want, in their heart of hearts, to know as soon as possible when breakthroughs are made - which is why I do at least two media interviews every WEEK even though I don't even do any experiments of my own. But that exposure to my work needs to be camouflaged as entertainment in order to be palatable.

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So, clearly, what I would dearly like to occur is for the media to have the guts to tell my story like it is, and to dare/embarrass/coerce their audience into thinking about it properly and then getting off their backsides and contributing whatever they can (money, activism, whatever) to the crusade to save 100,000 lives per day. But as I said, the journalists in question don't get paid to make their audience uncomfortable, so I'm not holding my breath.

Since any immune response to the presence of senescent cells may possibly be similar to that of cancer cells, the following is a brief outline describing the key points in the removal process (Ullrich et al, 2007, Vulink et al, 2008, Wesa and Storkus, 2008, Chan and Housseau, 2008).

Dendritic cells are antigen-presenting cells found in all tissues of the body and are crucial for stimulating a naïve T-lymphocyte response in the removal of tumour cells.

In the presence of tumour cells, dendritic cells capture (by engulfing portions of the tumour cell) and process tumour-specific molecules (antigens) so that they become presented on their cell surface. Dendritic cells start to mature as they migrate to the lymph nodes, a process which enables dendritic cells to present the tumour information. The maturation process is needed as additional co-stimulatory molecules are required so that they can be recognised by other immune cells. When mature dendritic cells reach the lymph nodes, they interact with cytotoxic T-lymphocytes (CTLs), and pass on the tumour information, causing CTLs to become activated and consequently proliferate. The large numbers of CTLs then circulate the body, recognising the tumour-specific antigens, binding to them and destroying tumour cells by the release of enzymes.

If a cancer cell (or a senescent cell) is not removed by the immune system, then something isn’t working as it should. From the brief overview above, there are a number of points between cell recognition and removal that could have failed. These are:

(1) Dendritic cells did not recognise the cancer/senescent cell.
(2) The dendritic cells did not display cancer/senescent specific markers on it’s surface.
(3) Lymphocytes were not activated in response to dendritic cells.

The changes which occur as we age which may have an impact on the removal of tumour cells/senescent cells will be discussed next.